Matrine Protects PC12 Cells Against Aβ25–35-Induced Cytotoxicity, Oxidative Stress, Inflammation, Neuronal Apoptosis and Cell Senescence

Abstract

Background and Objectives: Beta-amyloid (Aβ) has pivotal functions in the pathogenesis of Alzheimer’s Disease (AD). The main purpose of this study is to explore the protective role and possible mechanisms of matrine against Aβ25–35-induced neurotoxicity in PC12 cells. Materials and Methods: A vitro model that involved Aβ25–35-induced neuronal damage in PC12 cells was adopted in the present study. Cell viability and apoptosis of PC12 cells were determined by CCK-8 assay and TUNEL staining, respectively. Intracellular ROS levels were determined by DCFH-DA probe and levels of TNFα, IL-6 and IL-1β were assessed by ELISA assay. In addition, telomerase reverse transcriptase (TERT) levels were determined by ELISA assay and telomere lengths were examined by real-time quantitative PCR analysis to assess telomerase activities. Furthermore, vital proteins related to cell apoptosis and hallmarks of senescence were detected by western blot analysis. Results: Matrine (10, 20, 50 μg/ml) dose-dependently protected cell viability against Aβ25–35 cytotoxicity in PC12 cells. Meanwhile, matrine at 10, 20, 50 μg/ml markedly reduced ROS production and downregulated the levels of TNFα, IL-6 and IL-1β in Aβ25–35-injuried PC12 cells. The results also proved that matrine may restore telomerase activities and telomere lengths in Aβ25–35-injuried PC12 cells by inhibiting inflammatory responses and oxidative stress. Neuronal apoptosis induced by Aβ25–35 were reversed upon cotreatment with matrine. Moreover, matrine markedly mitigated Aβ25–35 induced cell senescence in a concentration-dependentmanner. Conclusion: Our findings demonstrated that matrine protected PC12 cells against Aβ25–35-induced cytotoxicity, oxidative stress, inflammation, neuronal apoptosis and cell senescence.